Peptide Vaccine for Glioblastoma Against Cytomegalovirus Antigens

NCT01854099 | Withdrawn Phase 1

• 1 other identifier: PERFORMANCE
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Eligible adult patients with new diagnosis of gliobastoma are enrolled to receive 3 weekly vaccinations of the study drug PEP-CMV 1-3 days following standard of care chemoradiation. Patients will then be randomized to one of three arms: 1). standard temozolomide (TMZ)(200mg/m\^2 for 5 days) with vaccine on day 6-8 of each monthly TMZ cycle. 2). standard TMZ (200mg/m\^2 for 5 days) with vaccine on day 22-24 of each monthly TMZ cycle. 3). dose-intensified TMZ (100 mg./m\^2 for 21 days) with vaccine on day 22-24 of each monthly cycle. All vaccines will be given intradermally (i.d.) and will be given with monthly TMZ cycles and continue after TMZ cycles until progression or death.

Conditions

Glioblastoma

Keywords

Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Safety

  To determine the optimal \& safe peptide vaccination regimen with TMZ through dose-limiting toxicity (DLT) measurements. The primary safety assessment for DLT will be determined 1 week after the 3rd weekly vaccine. A DLT will be defined as any irreversible Grade 3 toxicity, any Grade 4 toxicity, or any life threatening-event not attributable to concomitant medication, co-morbid event, or disease progression. Initially 6 patients will be accrued to the study (2 per arm) after which accrual will be suspended to review the toxicity experienced by these patients during the first 3 weekly vaccinations. If 0 or 1 of these patients experience DLT, accrual of the remaining patients will commence. Otherwise, modifications of the protocol will be considered before accruing additional patients.

  6 months

Study Arms (3)

5 Day TMZ with PEP-CMV on Day 6-8

ACTIVE COMPARATOR

Standard TMZ (200 mg/m2/day x 5 days) with PEP-CMV vaccination on Day 6-8 of each monthly TMZ cycle

Biological: PEP-CMV

5 day TMZ with vaccine on day 22-24

ACTIVE COMPARATOR

Standard TMZ (200 mg/m2/day x 5 days) with vaccination on Day 22-24 of each monthly TMZ cycle

Biological: PEP-CMV

21 day TMZ wtih vaccine on day 22-24

ACTIVE COMPARATOR

Dose-intensified TMZ (100 mg/m2/day x 21 days) with vaccination on day 22-24 of each monthly TMZ cycle

Biological: PEP-CMV

Interventions

PEP-CMV BIOLOGICAL

500 µg of PEP-CMV vaccine given intradermally on day 6-8 of each monthly TMZ cycle (standard 200 mg/m\^2 x 5 days) with group 1.

5 Day TMZ with PEP-CMV on Day 6-8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histopathologically proven newly-diagnosed primary glioblastoma multiforme.
• The tumor must have a supratentorial component.
• Patients must be CMV seropositive.
• Signed informed consent. If the patient's mental status precludes his/her giving informed consent, written informed consent may be given by the responsible family member or legal representative.
• For females of child-bearing potential, negative serum pregnancy test 48 hours prior to temozolomide.
• Women of childbearing potential and male participants must practice adequate contraception.
• Karnofsky performance status of ≥ 60.
• Patients must have recovered from the effects of surgery, postoperative infection, and other complications at time of enrollment.
• Prior to adjuvant TMZ:
• Patients must complete radiation therapy (RT) (60.0Gy over 6 weeks) and concomitant TMZ (targeted dose of 75mg/m2/d for \<49 days) therapy without significant toxicity that persisted over a duration of 4 weeks. Significant toxicity is defined as one or more of the following observations:
• Absolute neutrophil count (ANC) \< 0.5 x 109/L (Grade 4)
• Platelet count \< 10 x 109/L (Grade 4)
• Grade 3 or 4 non-hematologic adverse event (AE) (except alopecia, nausea and vomiting unless the patient has failed maximal antiemetic therapy, and fatigue).
• Documentation of stable or decreasing steroid dose prior to randomization with goal of minimizing steroid use.

You may not qualify if:

• Patients did not start RT and TMZ within 5 weeks of surgery.
• Patients that did not complete 60.0Gy over 6-7 weeks of RT (patients consented prior to completion who do not complete RT will be removed from study and replaced).
• Progression of disease prior to randomization as defined by RANO.
• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years. (For example, carcinoma in situ of the breast, oral cavity, and cervix are all permissible.)
• Metastases detected below the tentorium or beyond the cranial vault.
• Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the head and neck region (other than TMZ prescribed during radiation for glioblastoma); note that prior chemotherapy for a different cancer is allowable.
• Prior radiotherapy to the head or neck (except for T1 glottic cancer and that prescribed for GBM ≤60 Gy), resulting in overlap of radiation fields. Radiosurgery is not permitted.
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization.
• Transmural myocardial infarction within the last 6 months.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of beginning chemoradiation.
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of beginning chemoradiation.
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.

Sponsors & Collaborators

• University of Florida: lead
• American Brain Tumor Association: collaborator

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Duane A Mitchell, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2013
• First Posted: May 15, 2013
• Study Start: January 1, 2014
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 14, 2014

Record last verified: 2014-01